Annexin A6 contributes to the invasiveness of breast carcinoma cells by influencing the organization and localization of functional focal adhesions.
Annexin A6 contributes to the invasiveness of breast carcinoma cells by influencing the organization and localization of functional focal adhesions.
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DOI：
10.1016/j.yexcr.2010.12.008
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发表时间：
2011-04-01
影响因子：
3.7
通讯作者：
Ochieng J
中科院分区：
文献类型：
--
作者：
Sakwe AM;Koumangoye R;Guillory B;Ochieng J
膜联蛋白A6(AnxA6)与膜磷脂、特殊的细胞外基质成分或F-肌动蛋白的相互作用表明，它可能影响与快速质膜重组相关的细胞过程，如细胞黏附和运动。在这里，我们研究了AnxA6在促进乳腺癌进展的黏附相关细胞过程中的假定作用。我们发现乳腺癌细胞通过胞外途径分泌膜联蛋白，并且分泌的膜联蛋白主要与细胞表面相关。在侵袭性BT-549乳腺癌细胞中，AnxA6的缺失伴随着非贴壁细胞生长的增强，但细胞与细胞的粘附力、细胞在IV型胶原或胎球蛋白-A上的黏附/扩散、细胞的运动性和侵袭性受到强烈抑制。为了解释黏附/运动能力的丧失，我们证明了AnxA6缺失的BT-549细胞中基于纽蛋白的焦点黏附是拉长的和随机分布的。这些焦点接触也是功能缺陷的，因为粘着斑激酶和磷脂酰肌醇-3激酶/Akt通路的激活受到强烈抑制，而MAP激酶通路保持结构性活性。与正常乳腺组织相比，乳腺癌组织中AnxA6表达降低与细胞增殖增强相关。综上所述，这表明AnxA6表达的减少通过促进功能性细胞-细胞和/或细胞-ECM接触的丧失和锚定非依赖性细胞的增殖而促进乳腺癌的进展。
The interaction of annexin A6 (AnxA6) with membrane phospholipids and either specific extracellular matrix (ECM) components or F-actin suggests that it may influence cellular processes associated with rapid plasma membrane reorganization such as cell adhesion and motility. Here, we examined the putative roles of AnxA6 in adhesion-related cellular processes that contribute to breast cancer progression. We show that breast cancer cells secrete annexins via the exosomal pathway and that the secreted annexins are predominantly cell surface-associated. Depletion of AnxA6 in the invasive BT-549 breast cancer cells is accompanied by enhanced anchorage-independent cell growth but cell-cell cohesion, cell adhesion/spreading onto collagen type IV or fetuin-A, cell motility and invasiveness were strongly inhibited. To explain the loss in adhesion/motility, we show that vinculin-based focal adhesions in the AnxA6-depleted BT-549 cells are elongated and randomly distributed. These focal contacts are also functionally defective because the activation of focal adhesion kinase and the phosphoinositide-3 kinase/Akt pathway were strongly inhibited while the MAP kinase pathway remained constitutively active. Compared with normal human breast tissues, reduced AnxA6 expression in breast carcinoma tissues correlates with enhanced cell proliferation. Together this suggests that reduced AnxA6 expression contributes to breast cancer progression by promoting the loss of functional cell-cell and/or cell-ECM contacts and anchorage-independent cell proliferation.
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影响因子：
11.1
作者：
Maschler, Sabine;Gebeshuber, Christoph A.;Wiedemann, Eva-Maria;Alacakaptan, Memetcan;Schreiber, Martin;Custic, Ivana;Beug, Hartmut
通讯作者：
Beug, Hartmut
影响因子：
4.8
作者：
Bode, Guenther;Lueken, Aloys;Nacken, Wolfgang
通讯作者：
Nacken, Wolfgang
影响因子：
11.4
作者：
Hayes, Matthew J.;Shao, Dongmin;Moss, Stephen E.
通讯作者：
Moss, Stephen E.
影响因子：
4.8
作者：
Debnath, J;Muthuswamy, SK;Brugge, JS
通讯作者：
Brugge, JS
影响因子：
5.3
作者：
Heyraud, Stephanie;Jaquinod, Michel;Gulino-Debrac, Danielle
通讯作者：
Gulino-Debrac, Danielle